The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takeuchi, O.
Right arrow Articles by Akira, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takeuchi, O.
Right arrow Articles by Akira, S.
The Journal of Immunology, 2000, 165: 5392-5396.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: TLR2-Deficient and MyD88-Deficient Mice Are Highly Susceptible to Staphylococcus aureus Infection1

Osamu Takeuchi*,{dagger}, Katsuaki Hoshino*,{dagger} and Shizuo Akira2,*,{dagger}

* Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and {dagger} Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Osaka, Japan


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Toll-like receptor (TLR) family acts as pattern recognition receptors for pathogen-specific molecular patterns. We previously showed that TLR2 recognizes Gram-positive bacterial components whereas TLR4 recognizes LPS, a component of Gram-negative bacteria. MyD88 is shown to be an adaptor molecule essential for TLR family signaling. To investigate the role of TLR family in host defense against Gram-positive bacteria, we infected TLR2- and MyD88-deficient mice with Staphylococcus aureus. Both TLR2- and MyD88-deficient mice were highly susceptible to S. aureus infection, with more enhanced susceptibility in MyD88-deficient mice. Peritoneal macrophages from MyD88-deficient mice did not produce any detectable levels of cytokines in response to S. aureus. In contrast, TLR2-deficient macrophages produced reduced, but significant, levels of the cytokines, and TLR4-deficient macrophages produced the same amounts as wild-type cells, indicating that S. aureus is recognized not only by TLR2, but also by other TLR family members except for TLR4.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
A bacterial infection is one of the major causes of death even in the present day. Streptococcus aureus, a Gram-positive extracellular growing bacteria, is a major source of mortality in medical facilities (1). It causes a wide range of infections from skin infection to life-threatening diseases including abscesses of various organs, pneumonia, osteomyelitis, endocarditis, arthritis, and sepsis.

Initial host defense against bacterial infection is executed by innate immunity, characterized by the use of germline-encoded receptors for pathogen recognition (2). In Drosophila, Toll family plays a key role in antifungal and antibacterial host defense (3). Recently, mammalian homologues of Toll, designated as Toll-like receptors (TLRs),3 were discovered (4, 5, 6). Each TLR is a type I transmembrane receptor possessing an extracellular leucine-rich repeat and a cytoplasmic Toll/IL-1 receptor homology domain. They are expected to act as pattern recognition receptors, which distinguish pathogen-associated molecular patterns, such as LPS, peptidoglycan (PGN), and lipoprotein (2). Among TLR family members, both TLR2 and TLR4 have been shown to recognize bacterial components. A mutation in the Tlr4 gene is responsible for the phenotype of the C3H/HeJ mouse strain, which is unresponsiveness to LPS, a component of the outer membrane of Gram-negative bacteria (7). Targeted disruption of the Tlr4 gene resulted in abrogation of responses to LPS and lipoteichoic acid (8, 9). In contrast, TLR2 is implicated in the recognition of Gram-positive bacterial components, bacterial lipoproteins, and zymosan (10, 11, 12, 13, 14, 15). TLR2-deficient mice displayed impaired cytokine production in response to Staphylococcus aureus PGN preparation and mycoplasmal lipopeptide (9, 16).

MyD88 is a cytoplasmic adaptor molecule essential for the signaling of IL-1R/TLR family. Ligand binding to IL-1R/TLR family results in the recruitment of MyD88 to Toll/IL-1 receptor domains of receptors, which bridges the signal to IL-1R-associated kinase. Ultimately, the activation of a transcription factor NF-{kappa}B occurs and permits the transactivation of proinflammatory cytokine genes (17, 18). We have generated MyD88-deficient mice and shown that MyD88 is essential for cellular responses to IL-1, IL-18, and many bacterial cell wall components such as LPS, PGN, and lipopeptide (19, 20, 21).

C3H/HeJ mice are known to be highly sensitive to infection with Gram-negative bacteria, owing to the failure of LPS recognition (22). Although TLR2 participates in the recognition of Gram-positive bacteria, a substantial role of TLR2 in host defense against Gram-positive bacteria was still unclear. In the present study, we investigated the role of TLR2 and MyD88 in S. aureus infection using mutant mice deficient in these molecules.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Mice

The mutant mouse (F2 interbred from 129/Ola x C57BL/6) strains deficient in TLR2, TLR4, or MyD88 were generated by gene targeting as described previously (8, 9, 19). MyD88-deficient mice were backcrossed eight times with C57BL/6 mice. For S. aureus infection, groups of TLR2-deficient mice and wild-type littermates or MyD88-deficient mice (C57BL/6 background) and wild-type littermates were used. Age-matched groups of wild-type, TLR2-, TLR4-, and MyD88-deficient mice were used for the other experiment.

Bacteria and infection

S. aureus 834 strain (gift from A. Nakane, Hirosaki University, Japan) was classified as coagulase type II, produced toxic shock syndrome toxin I and methicillin resistant (23), and it was prepared as described previously (23, 24). In brief, bacteria were cultured on trypticase soy agar (Becton Dickinson, Sparks, MD), inoculated with trypticase soy broth, and incubated for 15 h at 37°C. The bacteria were collected and resuspended by PBS. The concentration of resuspended cells was adjusted spectrophotometrically at 550 nm. Mice were given i.v. injections of 0.2 ml of bacterial solution containing 1 x 107 CFU of viable S. aureus and their survival was monitored for up to 14 days. S. aureus suspension (1 x 109 CFU/ml in PBS) was boiled for 30 min and used as heat-killed S. aureus.

Determination of the number of bacteria in blood and organs

Mice were given 1 x 107 CFU or 1 x 106 CFU of S. aureus as an i.v. infection, and they were killed 1, 2, or 5 days later. Spleens and kidneys were dissected, homogenized, and diluted in 10-fold steps in sterile water containing 0.5% Triton X-100 (Nacalai Tesque, Kyoto, Japan). Blood was also diluted in water containing 0.5% Triton X-100. Bacterial CFU was determined by plating each dilution on trypticase soy agar and was cultured for 24 h at 37°C.

Preparation of peritoneal macrophages

Mice were i.p. injected with 2 ml of 4% thioglycolate (Difco, Detroit, MI). Three days later, peritoneal exudate cells were isolated from the peritoneal cavity by washing with ice-cold HBSS (Life Technologies, Rockville, MD). Cells were cultured for 2 h and washed with HBSS to remove nonadherent cells. Adherent monolayer cells were used as peritoneal macrophages. Peritoneal macrophages (5 x 105/ml) were cultured in RPMI 1640 medium (Nacalai Tesque) supplemented with 10% FCS and stimulated with 1 x 107 CFU/ml of heat-killed S. aureus for 24 h. Concentration of TNF-{alpha} in culture supernatant was determined by ELISA (Genzyme Techne, Minneapolis, MN) and IL-6 concentration was also measured by ELISA (Endogen, Boston, MA).

Statistical analysis

Kaplan-Meier plots were conducted and the log rank test was used to test the differences in the survival between wild-type and TLR2-deficient or MyD88-deificient mice. The significances of the difference between the groups in the numbers of bacteria and cytokine concentrations were tested using Mann-Whitney U test.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Decreased survival of TLR2-deficient mice after infection with S. aureus

We have previously shown that TLR2 is required for the recognition of PGN from S. aureus. Moreover, TLR2-deficient macrophages did not produce TNF-{alpha} in response to cell wall preparation from S. aureus (9). To evaluate the in vivo role of TLR2 against S. aureus infection, wild-type and TLR2-deficient mice were infected i.v. with 1 x 107 CFU of S. aureus and their survival was monitored. As shown in Fig. 1Go, all wild-type mice survived for 8 days after S. aureus inoculation and 60% survived on day 14. In contrast, about 80% of TLR2-deficient mice succumbed to S. aureus and died within 8 days, and only 10% survived on day 14 (p < 0.03). However, when a low dose (1 x 106 CFU) of S. aureus was administered in the mice, the survival was not altered between wild-type and TLR2-deficient mice (data not shown). To investigate whether this susceptibility was the result of altered bacterial distribution and growth in vivo, the bacterial numbers in the blood, spleen, and kidney of mice were determined at 1 and 2 days after 1 x 107 CFU of S. aureus infection. At both 1 and 2 days, the number of S. aureus in the blood and kidney were higher in TLR2-deficient mice, consistent with high morbidity and mortality of TLR2-deficient mice after infection with S. aureus (Fig. 2GoA). When the mice were inoculated with 1 x 106 CFU of S. aureus, a statistically significant difference was not observed in the bacterial numbers between wild-type and TLR2-deficient organs at both 2 and 5 days after inoculum (Fig. 2GoB).



View larger version (14K):
[in this window]
[in a new window]
  		FIGURE 1. Survival of TLR2-deficient mice (n = 10, {blacksquare}) and wild-type mice (n = 10, {circ}) after i.v. infection of 1 x 107 CFU of S. aureus. p < 0.03 in log rank test.

 


View larger version (31K):
[in this window]
[in a new window]
  		FIGURE 2. Numbers of live S. aureus in TLR2-deficient and wild-type mice after injection of bacteria. TLR2-deficient mice (n = 4 or 5) and wild-type mice (n = 4 or 5) were infected i.v. with 1 x 107 CFU (A) or 1 x 106 CFU (B) S. aureus. The blood and organs were collected 1 and 2 days (A) or 2 and 5 days (B) after injection, and bacterial counts were determined by culture on agar. Data are represented as the mean number of CFU ± SD. *, p < 0.05 in Mann-Whitney U test.

 
High susceptibility of MyD88-deficient mice to S. aureus infection

MyD88 is an adaptor molecule essential for the signaling of the IL-1R/TLR family. We have previously shown that MyD88-deficient mice lacked responsiveness to IL-1, IL-18, and LPS (19, 20). S. aureus PGN-induced TNF-{alpha} production was also abrogated in MyD88-deficient macrophages, indicating the role of MyD88 in anti-Gram-positive bacterial host defense (21). Therefore, we infected MyD88-deficient mice with S. aureus and monitored their survival. After inoculation with 1 x 107 S. aureus, all MyD88-deficient mice succumbed to infection and died within 5 days, whereas 80% of wild-type mice survived for 14 days (p < 0.0003,Fig. 3Go). MyD88-deficient mice died more rapidly than TLR2-deficient mice. Next, the number of bacterial cells in the blood, spleen, and kidney were determined at 1 day of 1 x 107 CFU S. aureus infection. Bacterial numbers in the blood and kidney were increased in MyD88-deficient mice compared with wild-type mice (Fig. 4GoA). Even when the mice were inoculated with a lower dose of bacteria (1 x 106 CFU), the bacterial numbers in the organs from MyD88-deficient mice were significantly higher than those from wild-type mice (Fig. 4GoB). These results indicate that MyD88-deficient mice are more susceptible to S. aureus infection than TLR2-deficient mice.



View larger version (12K):
[in this window]
[in a new window]
  		FIGURE 3. Survival of MyD88-deficient mice (n = 10, {circ}) and wild-type mice (n = 10, {blacksquare}) after i.v. infection of 1 x 107 CFU of S. aureus. p < 0.0003 in log rank test.

 


View larger version (33K):
[in this window]
[in a new window]
  		FIGURE 4. Numbers of live S. aureus in MyD88-deficient and wild-type mice after injection of bacteria. MyD88-deficient mice (n = 3 or 4) and wild-type mice (n = 3 or 4) were infected i.v. with 1 x 107 CFU (A) or 1 x 106 CFU (B) S. aureus. The blood and organs were collected 1 (A) or 2 days and 5 days (B) after injection, and bacterial counts were determined by culture on agar. Data are represented as the mean number of CFU ± SD. *, p < 0.05 in Mann-Whitney U test.

 
Role of TLR2 and MyD88 in the cytokines production in response to heat-killed S. aureus

Furthermore, we examined the responsiveness of peritoneal macrophages from wild-type, TLR2-, and MyD88-deficient mice to heat-killed S. aureus. Thioglycolate-elicited peritoneal macrophages were cultured in the presence of 1 x 107 CFU/ml of S. aureus for 24 h, and concentrations of TNF-{alpha} and IL-6 in culture supernatant were measured. Macrophages from wild-type and TLR4-deficient mice produced almost the same amount of TNF-{alpha} in response to heat-killed S. aureus. TLR2-deficient macrophages produced a reduced, but significant level of TNF-{alpha}. In contrast, MyD88-deficient macrophages did not produce any detectable TNF-{alpha} (Fig. 5GoA). IL-6 production in response to S. aureus was also reduced in TLR2-deficient macrophages and abrogated in MyD88-deficient macrophages (Fig. 5GoB).



View larger version (21K):
[in this window]
[in a new window]
  		FIGURE 5. Production of TNF-{alpha} and IL-6 in response to heat-killed S. aureus in TLR2-, TLR4-, and MyD88-deficient macrophages. Peritoneal macrophages from wild-type, TLR2-, TLR4-, and MyD88-deficient mice were cultured in the presence of 1 x 107 CFU/ml of heat-killed S. aureus for 24 h. Concentrations of TNF-{alpha} (A) and IL-6 (B) in the culture supernatants were measured by ELISA. The results are representative of three independent experiments and are shown as the mean ± SEM of triplicate wells. *, p < 0.05 in Mann-Whitney U test. N.D., Not detected.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The present study demonstrated the critical role of TLR2 and MyD88 against extracellular Gram-positive bacteria using knockout mice. Both TLR2- and MyD88-deficient mice developed higher mortality compared with wild-type mice after inoculation with S. aureus. These are associated with a bacterial growth in the blood and kidney. We have previously shown that S. aureus PGN-induced cytokine production was dependent on TLR2 (9). Thus, failure of recognizing invading bacteria is responsible for high susceptibility in TLR2-deficient mice. It was reported that C3H/HeJ mice, possessing a point mutation in the Tlr4 gene, are highly susceptible to infection with Salmonella typhimurium. LD50 value of the bacteria for C3H/HeJ mouse strain was <2, in contrast to the resistance of C3H/HeN mice to S. typhimurium infection (LD50 = 1 x 104) (22). These observations indicate the distinct roles of TLR2 and TLR4 in discriminating invading pathogens.

MyD88-deficient mice were also highly susceptible to S. aureus infection and they were more susceptible to infection than TLR2-deficient mice. We have shown that MyD88-deficient mice display the defective response to many bacterial components and IL-1 family cytokines such as IL-1 and IL-18 (19). Both severely impaired bacterial recognition and failure of signaling mediated by IL-1 family cytokines may contribute to the susceptibility of MyD88-deficient mice to infection.

We have previously shown that S. aureus cell wall-mediated TNF-{alpha} production was fully TLR2 dependent (9). Therefore, it was surprising that the production of proinflammatory cytokine was induced in response to heat-killed S. aureus in TLR2-deficient macrophages, although the level was reduced compared with that in wild-type macrophages. In contrast, bacteria-mediated TNF-{alpha} production was abrogated in MyD88-deficient cells. Although TLR4-deficient macrophages displayed impaired responsiveness to Gram-positive lipoteichoic acids, TLR4-deficient macrophages re-sponded to heat-killed S. aureus to the same extent as wild-type cells, indicating that lipoteichoic acid on S. aureus cell surfaces may not significantly contribute to cellular activations. These results suggest that S. aureus is recognized not only by TLR2, but also by other TLR/IL-1R family members except for TLR4. A previous report demonstrated that the treatment with anti-TNF-{alpha} Ab to mice after inoculation of S. aureus increased the death rate (23). Our results also indicate the correlation between the S. aureus-induced TNF-{alpha} production and the resistance of mice to the infection.

Taken together, innate recognition of bacteria by TLR family members is quite important for eliminating invading bacteria. Particularly, TLR2 plays a crucial role in host defense against extracellular growing Gram-positive bacteria. Similarly, high mortality after S. aureus infection and complete abrogation of proinflammatory cytokine secretion in MyD88-deficient mice shows an essential role of MyD88 in resistance to Gram-positive bacterial infection.


   Acknowledgments
 
We thank Dr. Akio Nakane for providing S. aureus 834 strain, Dr. Yoshihumi Takeda for helpful suggestions, and Dr. Hiroko Tsutsui for providing mice. We thank T. Aoki for excellent secretarial assistance and N. Tsuji and E. Nakatani for excellent technical assistance.


   Footnotes
 
1 This work was supported by grants from the Ministry of Education of Japan. Back

2 Address correspondence and reprint requests to Dr. Shizuo Akira, Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Back

3 Abbreviations used in this paper: TLR, Toll-like receptor; PGN, peptidoglycan. Back

Received for publication May 31, 2000. Accepted for publication September 13, 2000.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Lowy, F. D.. 1998. Staphylococcus aureus infections. N. Engl. J. Med. 339:520.[Free Full Text]
  2. Medzhitov, R., Jr C. A. Janeway. 1997. Innate immunity: the virtues of a monclonal system of recognition. Cell 91:295.[Medline]
  3. Kopp, E. B., R. Medzhitov. 1999. The Toll-receptor family and control of innate immunity. Curr. Opin. Immunol. 11:13.[Medline]
  4. Medzhitov, R., P. Preston-Hurburt, Jr C. A. Janeway. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394.[Medline]
  5. Rock, F. L., G. Hardiman, J. C. Timans, R. A. Kastelein, J. F. Bazan. 1998. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95:588.[Abstract/Free Full Text]
  6. Takeuchi, O., T. Kawai, H. Sanjo, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, K. Takeda, S. Akira. 1999. TLR6: a novel member of an expanding Toll-like receptor family. Gene 231:59.[Medline]
  7. Poltorak, A., X. He, I. Smirnova, M.-Y. Liu, C. V. Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, et al 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085.[Abstract/Free Full Text]
  8. Hoshino, K., O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa, Y. Takeda, K. Takeda, S. Akira. 1999. TLR4-deficient mice are hyporesponsive to LPS: evidence for TLR4 as the Lps gene product. J. Immunol. 162:3749.[Abstract/Free Full Text]
  9. Takeuchi, O., K. Hoshino, T. Kawai, H. Sanjo, T. Ogawa, H. Takada, K. Takeda, S. Akira. 1999. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11:443.[Medline]
  10. Schwandner, R., Dziarski, R., Wesche, H., Rothe, M., and Kirschning, C. J. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J. Biol. Chem. 274:17406.
  11. Yoshimura, A., E. Lien, R. R. Ingalls, E. Tuomanen, R. Dziarski, D. Golenbock. 1999. Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163:1.[Abstract/Free Full Text]
  12. Brightbill, D. H., H. D. Libraty, R. S. Krutzik, B. R. Yang, T. J. Belisle, R. J. Bleharski, M. Maitland, V. M. Norgard, E. S. Plevy, T. S. Smale, et al 1999. Host defense mechanisms triggered by microbial lipoproteins through Toll-Like receptors. Science 285:732.[Abstract/Free Full Text]
  13. Aliprantis, O. A., R. B. Yang, R. M. Mark, S. Suggett, B. Devaux, D. J. Radolf, R. G. Klimpel, P. Godowski, A. Zychlinsky. 1999. Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 285:736.[Abstract/Free Full Text]
  14. Lien, E., T. J. Sellati, A. Yoshimura, T. H. Flo, G. Rawadi, R. W. Finberg, J. D. Carroll, T. Espevik, R. R. Ingalls, J. D. Radolf, D. T. Golenbock. 1999. Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J. Biol. Chem. 274:33419.[Abstract/Free Full Text]
  15. Underhill, D. M., A. Ozinsky, A. M. Hajjar, A. Stevens, C. B. Wilson, M. Bassetti, A. Aderem. 1999. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401:811.[Medline]
  16. Takeuchi, O., A. Kaufmann, K. Grote, T. Kawai, K. Hoshino, M. Morr, P. F. Muhlradt, S. Akira. 2000. Preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a Toll-like receptor 2- and MyD88-dependent signaling pathway. J. Immunol. 164:554.[Abstract/Free Full Text]
  17. Muzio, M., G. Natoli, S. Saccani, M. Levrero, A. Mantovani. 1998. The human Toll signaling pathway: divergence of nuclear factor {kappa}B and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J. Exp. Med. 187:2097.[Abstract/Free Full Text]
  18. Medzhitov, R., P. Preston-Hurlburt, E. Kopp, A. Stadlen, C. Chen, S. Ghosh, Jr C. A. Janeway. 1998. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 2:253.[Medline]
  19. Adachi, O., T. Kawai, K. Takeda, M. Matsumoto, H. Tsutsui, M. Sakagami, K. Nakanishi, S. Akira. 1998. Targeted disruption of the MyD 88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9:143.[Medline]
  20. Kawai, T., O. Adachi, T. Ogawa, K. Takeda, S. Akira. 1999. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11:115.[Medline]
  21. Takeuchi, O., K. Takeda, K. Hoshino, O. Adachi, T. Ogawa, S. Akira. 2000. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int, Immunol. 12:113.[Abstract/Free Full Text]
  22. O’Brien, A. D., D. L. Rosenstreich, I. Scher, G. H. Campbell, R. P. MacDermott, S. B. Formal. 1980. Genetic control of susceptibility to Salmonella typhimurium in mice: role of the LPS gene. J. Immunol. 124:20.[Medline]
  23. Nakane, A., M. Okamoto, M. Asano, M. Kohanawa, T. Minagawa. 1995. Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice. Infect. Immun. 63:1165.[Abstract]
  24. Sasaki, S., T. Miura, S. Nishikawa, K. Yamada, M. Hirasue, A. Nakane. 1998. Protective role of nitric oxide in Staphylococcus aureus infection in mice. Infect. Immun. 66:1017.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Infect. Immun.Home page
B. B. Mishra, U. M. Gundra, K. Wong, and J. M. Teale
MyD88-Deficient Mice Exhibit Decreased Parasite-Induced Immune Responses but Reduced Disease Severity in a Murine Model of Neurocysticercosis
Infect. Immun., December 1, 2009; 77(12): 5369 - 5379.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Sasaki, M. Ogasawara, T. Sekiguchi, S. Kusumoto, and H. Satake
Toll-like Receptors of the Ascidian Ciona intestinalis: PROTOTYPES WITH HYBRID FUNCTIONALITIES OF VERTEBRATE TOLL-LIKE RECEPTORS
J. Biol. Chem., October 2, 2009; 284(40): 27336 - 27343.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Munoz-Planillo, L. Franchi, L. S. Miller, and G. Nunez
A Critical Role for Hemolysins and Bacterial Lipoproteins in Staphylococcus aureus-Induced Activation of the Nlrp3 Inflammasome
J. Immunol., September 15, 2009; 183(6): 3942 - 3948.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
Y.-L. Cheng, C.-Y. Wang, W.-C. Huang, C.-C. Tsai, C.-L. Chen, C.-F. Shen, C.-Y. Chi, and C.-F. Lin
Staphylococcus aureus Induces Microglial Inflammation via a Glycogen Synthase Kinase 3{beta}-Regulated Pathway
Infect. Immun., September 1, 2009; 77(9): 4002 - 4008.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
Y.-C. Chang, W.-C. Kao, W.-Y. Wang, W.-Y. Wang, R.-B. Yang, and K. Peck
Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses
FASEB J, September 1, 2009; 23(9): 3078 - 3088.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Chamorro, J. J. Garcia-Vallejo, W. W. J. Unger, R. J. Fernandes, S. C. M. Bruijns, S. Laban, B. O. Roep, B. A. 't Hart, and Y. van Kooyk
TLR Triggering on Tolerogenic Dendritic Cells Results in TLR2 Up-Regulation and a Reduced Proinflammatory Immune Program
J. Immunol., September 1, 2009; 183(5): 2984 - 2994.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Chassin, M. Picardeau, J.-M. Goujon, P. Bourhy, N. Quellard, S. Darche, E. Badell, M. F. d'Andon, N. Winter, S. Lacroix-Lamande, et al.
TLR4- and TLR2-Mediated B Cell Responses Control the Clearance of the Bacterial Pathogen, Leptospira interrogans
J. Immunol., August 15, 2009; 183(4): 2669 - 2677.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. Hruz, A. S. Zinkernagel, G. Jenikova, G. J. Botwin, J.-P. Hugot, M. Karin, V. Nizet, and L. Eckmann
NOD2 contributes to cutaneous defense against Staphylococcus aureus through {alpha}-toxin-dependent innate immune activation
PNAS, August 4, 2009; 106(31): 12873 - 12878.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
E. Slack, S. Hapfelmeier, B. Stecher, Y. Velykoredko, M. Stoel, M. A. E. Lawson, M. B. Geuking, B. Beutler, T. F. Tedder, W.-D. Hardt, et al.
Innate and Adaptive Immunity Cooperate Flexibly to Maintain Host-Microbiota Mutualism
Science, July 31, 2009; 325(5940): 617 - 620.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
F. Han, H. Yu, C. Tian, S. Li, M. R. Jacobs, C. Benedict-Alderfer, and Q. Y. Zheng
Role for Toll-Like Receptor 2 in the Immune Response to Streptococcus pneumoniae Infection in Mouse Otitis Media
Infect. Immun., July 1, 2009; 77(7): 3100 - 3108.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
Y. Minegishi, M. Saito, M. Nagasawa, H. Takada, T. Hara, S. Tsuchiya, K. Agematsu, M. Yamada, N. Kawamura, T. Ariga, et al.
Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome
J. Exp. Med., June 8, 2009; 206(6): 1291 - 1301.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. Kenzel, S. Santos-Sierra, S. D. Deshmukh, I. Moeller, B. Ergin, K. A. Fitzgerald, E. Lien, S. Akira, D. T. Golenbock, and P. Henneke
Role of p38 and Early Growth Response Factor 1 in the Macrophage Response to Group B Streptococcus
Infect. Immun., June 1, 2009; 77(6): 2474 - 2481.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Schmaler, N. J. Jann, F. Ferracin, L. Z. Landolt, L. Biswas, F. Gotz, and R. Landmann
Lipoproteins in Staphylococcus aureus Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo
J. Immunol., June 1, 2009; 182(11): 7110 - 7118.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. R. Nichols, A. L. Aldrich, M. M. Mariani, D. Vidlak, N. Esen, and T. Kielian
TLR2 Deficiency Leads to Increased Th17 Infiltrates in Experimental Brain Abscesses
J. Immunol., June 1, 2009; 182(11): 7119 - 7130.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
L. A. J. O'Neill, C. E. Bryant, and S. L. Doyle
Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer
Pharmacol. Rev., June 1, 2009; 61(2): 177 - 197.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
T. H. Mogensen
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
Clin. Microbiol. Rev., April 1, 2009; 22(2): 240 - 273.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Puliti, S. Uematsu, S. Akira, F. Bistoni, and L. Tissi
Toll-Like Receptor 2 Deficiency Is Associated with Enhanced Severity of Group B Streptococcal Disease
Infect. Immun., April 1, 2009; 77(4): 1524 - 1531.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. Amiel, A. Alonso, S. Uematsu, S. Akira, M. E. Poynter, and B. Berwin
Pivotal Advance: Toll-like receptor regulation of scavenger receptor-A-mediated phagocytosis
J. Leukoc. Biol., April 1, 2009; 85(4): 595 - 605.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Kurokawa, H. Lee, K.-B. Roh, M. Asanuma, Y. S. Kim, H. Nakayama, A. Shiratsuchi, Y. Choi, O. Takeuchi, H. J. Kang, et al.
The Triacylated ATP Binding Cluster Transporter Substrate-binding Lipoprotein of Staphylococcus aureus Functions as a Native Ligand for Toll-like Receptor 2
J. Biol. Chem., March 27, 2009; 284(13): 8406 - 8411.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. C. Alves-Filho, A. Freitas, F. O. Souto, F. Spiller, H. Paula-Neto, J. S. Silva, R. T. Gazzinelli, M. M. Teixeira, S. H. Ferreira, and F. Q. Cunha
Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis
PNAS, March 10, 2009; 106(10): 4018 - 4023.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Roger, C. Froidevaux, D. Le Roy, M. K. Reymond, A.-L. Chanson, D. Mauri, K. Burns, B. M. Riederer, S. Akira, and T. Calandra
Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4
PNAS, February 17, 2009; 106(7): 2348 - 2352.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. N. Sorensen, L. S. Reinert, L. Malmgaard, C. Bartholdy, A. R. Thomsen, and S. R. Paludan
TLR2 and TLR9 Synergistically Control Herpes Simplex Virus Infection in the Brain
J. Immunol., December 15, 2008; 181(12): 8604 - 8612.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
C. M. Rocha-de-Souza, B. Berent-Maoz, D. Mankuta, A. E. Moses, and F. Levi-Schaffer
Human Mast Cell Activation by Staphylococcus aureus: Interleukin-8 and Tumor Necrosis Factor Alpha Release and the Role of Toll-Like Receptor 2 and CD48 Molecules
Infect. Immun., October 1, 2008; 76(10): 4489 - 4497.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. Miettinen, V. Veckman, S. Latvala, T. Sareneva, S. Matikainen, and I. Julkunen
Live Lactobacillus rhamnosus and Streptococcus pyogenes differentially regulate Toll-like receptor (TLR) gene expression in human primary macrophages
J. Leukoc. Biol., October 1, 2008; 84(4): 1092 - 1100.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. Sukhumavasi, C. E. Egan, A. L. Warren, G. A. Taylor, B. A. Fox, D. J. Bzik, and E. Y. Denkers
TLR Adaptor MyD88 Is Essential for Pathogen Control during Oral Toxoplasma gondii Infection but Not Adaptive Immunity Induced by a Vaccine Strain of the Parasite
J. Immunol., September 1, 2008; 181(5): 3464 - 3473.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Hussain, N. Nasreen, Y. Lai, B. F. Bellew, V. B. Antony, and K. A. Mohammed
Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2 dependent induction of {beta}-defensin-2 by staphylococcal peptidoglycan
Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L461 - L470.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
H. von Bernuth, C. Picard, Z. Jin, R. Pankla, H. Xiao, C.-L. Ku, M. Chrabieh, I. B. Mustapha, P. Ghandil, Y. Camcioglu, et al.
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency
Science, August 1, 2008; 321(5889): 691 - 696.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Piccini, S. Carta, S. Tassi, D. Lasiglie, G. Fossati, and A. Rubartelli
ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1{beta} and IL-18 secretion in an autocrine way
PNAS, June 10, 2008; 105(23): 8067 - 8072.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
O. S. Shin, R. R. Isberg, S. Akira, S. Uematsu, A. K. Behera, and L. T. Hu
Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis of Borrelia burgdorferi and Cytokine Induction
Infect. Immun., June 1, 2008; 76(6): 2341 - 2351.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
B. Pang, D. Winn, R. Johnson, W. Hong, S. West-Barnette, N. Kock, and W. E. Swords
Lipooligosaccharides Containing Phosphorylcholine Delay Pulmonary Clearance of Nontypeable Haemophilus influenzae
Infect. Immun., May 1, 2008; 76(5): 2037 - 2043.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
S. C. Nance, A.-K. Yi, F. C. Re, and E. A. Fitzpatrick
MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis
J. Leukoc. Biol., May 1, 2008; 83(5): 1207 - 1217.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Lampropoulou, K. Hoehlig, T. Roch, P. Neves, E. C. Gomez, C. H. Sweenie, Y. Hao, A. A. Freitas, U. Steinhoff, S. M. Anderton, et al.
TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity
J. Immunol., April 1, 2008; 180(7): 4763 - 4773.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Leendertse, R. J. L. Willems, I. A. J. Giebelen, P. S. van den Pangaart, W. J. Wiersinga, A. F. de Vos, S. Florquin, M. J. M. Bonten, and T. van der Poll
TLR2-Dependent MyD88 Signaling Contributes to Early Host Defense in Murine Enterococcus faecium Peritonitis
J. Immunol., April 1, 2008; 180(7): 4865 - 4874.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
K. Koga and G. Mor
Review Article: Expression and Function of Toll-Like Receptors at the Maternal--Fetal Interface
Reproductive Sciences, March 1, 2008; 15(3): 231 - 242.
[Abstract] [PDF]

Home page
 JEMHome page
W.K. E. Ip, K. Takahashi, K. J. Moore, L. M. Stuart, and R. A. B. Ezekowitz
Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome
J. Exp. Med., January 21, 2008; 205(1): 169 - 181.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H. S. Seo, S. M. Michalek, and M. H. Nahm
Lipoteichoic Acid Is Important in Innate Immune Responses to Gram-Positive Bacteria
Infect. Immun., January 1, 2008; 76(1): 206 - 213.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
W. Stenzel, S. Soltek, M. Sanchez-Ruiz, S. Akira, H. Miletic, D. Schluter, and M. Deckert
Both TLR2 and TLR4 Are Required for the Effective Immune Response in Staphylococcus aureus-Induced Experimental Murine Brain Abscess
Am. J. Pathol., January 1, 2008; 172(1): 132 - 145.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. E. Wisse, K. Ogimoto, J. Tang, M. K. Harris Jr., E. W. Raines, and M. W. Schwartz
Evidence that Lipopolysaccharide-Induced Anorexia Depends upon Central, Rather than Peripheral, Inflammatory Signals
Endocrinology, November 1, 2007; 148(11): 5230 - 5237.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. W. Haden, H. B. Suliman, M. S. Carraway, K. E. Welty-Wolf, A. S. Ali, H. Shitara, H. Yonekawa, and C. A. Piantadosi
Mitochondrial Biogenesis Restores Oxidative Metabolism during Staphylococcus aureus Sepsis
Am. J. Respir. Crit. Care Med., October 15, 2007; 176(8): 768 - 777.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C.-L. Ku, H. von Bernuth, C. Picard, S.-Y. Zhang, H.-H. Chang, K. Yang, M. Chrabieh, A. C. Issekutz, C. K. Cunningham, J. Gallin, et al.
Selective predisposition to bacterial infections in IRAK-4 deficient children: IRAK-4 dependent TLRs are otherwise redundant in protective immunity
J. Exp. Med., October 1, 2007; 204(10): 2407 - 2422.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
B. Csoka, Z. H. Nemeth, L. Virag, P. Gergely, S. J. Leibovich, P. Pacher, C.-X. Sun, M. R. Blackburn, E. S. Vizi, E. A. Deitch, et al.
A2A adenosine receptors and C/EBP{beta} are crucially required for IL-10 production by macrophages exposed to Escherichia coli
Blood, October 1, 2007; 110(7): 2685 - 2695.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
L. E. Cole, K. A. Shirey, E. Barry, A. Santiago, P. Rallabhandi, K. L. Elkins, A. C. Puche, S. M. Michalek, and S. N. Vogel
Toll-Like Receptor 2-Mediated Signaling Requirements for Francisella tularensis Live Vaccine Strain Infection of Murine Macrophages
Infect. Immun., August 1, 2007; 75(8): 4127 - 4137.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
V. Auerbuch and R. R. Isberg
Growth of Yersinia pseudotuberculosis in Mice Occurs Independently of Toll-Like Receptor 2 Expression and Induction of Interleukin-10
Infect. Immun., July 1, 2007; 75(7): 3561 - 3570.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Genestier, M. Taillardet, P. Mondiere, H. Gheit, C. Bella, and T. Defrance
TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses
J. Immunol., June 15, 2007; 178(12): 7779 - 7786.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Kim, M. A. Kim, I.-H. Cho, M. S. Kim, S. Lee, E.-K. Jo, S.-Y. Choi, K. Park, J. S. Kim, S. Akira, et al.
A Critical Role of Toll-like Receptor 2 in Nerve Injury-induced Spinal Cord Glial Cell Activation and Pain Hypersensitivity
J. Biol. Chem., May 18, 2007; 282(20): 14975 - 14983.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
O. Hoffmann, J. S. Braun, D. Becker, A. Halle, D. Freyer, E. Dagand, S. Lehnardt, and J. R. Weber
TLR2 Mediates Neuroinflammation and Neuronal Damage
J. Immunol., May 15, 2007; 178(10): 6476 - 6481.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
N. Chaudhuri, M. K. B. Whyte, and I. Sabroe
Reducing the Toll of Inflammatory Lung Disease
Chest, May 1, 2007; 131(5): 1550 - 1556.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. C. Dessing, K. F. van der Sluijs, S. Florquin, S. Akira, and T. van der Poll
Toll-Like Receptor 2 Does Not Contribute to Host Response during Postinfluenza Pneumococcal Pneumonia
Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 609 - 614.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
R. KuoLee, X. Zhao, J. Austin, G. Harris, J. W. Conlan, and W. Chen
Mouse Model of Oral Infection with Virulent Type A Francisella tularensis
Infect. Immun., April 1, 2007; 75(4): 1651 - 1660.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Nakayama, D. M. Underhill, T. W. Petersen, B. Li, T. Kitamura, T. Takai, and A. Aderem
Paired Ig-Like Receptors Bind to Bacteria and Shape TLR-Mediated Cytokine Production
J. Immunol., April 1, 2007; 178(7): 4250 - 4259.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Kielian, N. K. Phulwani, N. Esen, M. Md. Syed, A. C. Haney, K. McCastlain, and J. Johnson
MyD88-Dependent Signals Are Essential for the Host Immune Response in Experimental Brain Abscess
J. Immunol., April 1, 2007; 178(7): 4528 - 4537.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
R. Kapetanovic, M.-A. Nahori, V. Balloy, C. Fitting, D. J. Philpott, J.-M. Cavaillon, and M. Adib-Conquy
Contribution of Phagocytosis and Intracellular Sensing for Cytokine Production by Staphylococcus aureus-Activated Macrophages
Infect. Immun., February 1, 2007; 75(2): 830 - 837.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
F. Cao, A. Castrillo, P. Tontonoz, F. Re, and G. I. Byrne
Chlamydia pneumoniae-Induced Macrophage Foam Cell Formation Is Mediated by Toll-Like Receptor 2
Infect. Immun., February 1, 2007; 75(2): 753 - 759.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. J. Skerrett, C. B. Wilson, H. D. Liggitt, and A. M. Hajjar
Redundant Toll-like receptor signaling in the pulmonary host response to Pseudomonas aeruginosa
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L312 - L322.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. S. Hardarson, J. S. Baker, Z. Yang, E. Purevjav, C.-H. Huang, L. Alexopoulou, N. Li, R. A. Flavell, N. E. Bowles, and J. G. Vallejo
Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H251 - H258.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Burns, G. Bachrach, L. Shapira, and G. Nussbaum
Cutting Edge: TLR2 Is Required for the Innate Response to Porphyromonas gingivalis: Activation Leads to Bacterial Persistence and TLR2 Deficiency Attenuates Induced Alveolar Bone Resorption
J. Immunol., December 15, 2006; 177(12): 8296 - 8300.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
D. D. Bolz, R. S. Sundsbak, Y. Ma, S. Akira, J. H. Weis, T. G. Schwan, and J. J. Weis
Dual Role of MyD88 in Rapid Clearance of Relapsing Fever Borrelia spp.
Infect. Immun., December 1, 2006; 74(12): 6750 - 6760.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Flacher, M. Bouschbacher, E. Verronese, C. Massacrier, V. Sisirak, O. Berthier-Vergnes, B. de Saint-Vis, C. Caux, C. Dezutter-Dambuyant, S. Lebecque, et al.
Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria
J. Immunol., December 1, 2006; 177(11): 7959 - 7967.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. C. Mullaly and P. Kubes
The Role of TLR2 In Vivo following Challenge with Staphylococcus aureus and Prototypic Ligands
J. Immunol., December 1, 2006; 177(11): 8154 - 8163.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. M. Buckley, J. H. Wang, and H. P. Redmond
Cellular reprogramming by gram-positive bacterial components: a review
J. Leukoc. Biol., October 1, 2006; 80(4): 731 - 741.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Bubeck Wardenburg, W. A. Williams, and D. Missiakas
Host defenses against Staphylococcus aureus infection require recognition of bacterial lipoproteins
PNAS, September 12, 2006; 103(37): 13831 - 13836.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
Y. Sun, A. G. Hise, C. M. Kalsow, and E. Pearlman
Staphylococcus aureus-Induced Corneal Inflammation Is Dependent on Toll-Like Receptor 2 and Myeloid Differentiation Factor 88
Infect. Immun., September 1, 2006; 74(9): 5325 - 5332.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Mikami, J. H. Lim, H. Ishinaga, U.-H. Ha, H. Gu, T. Koga, H. Jono, H. Kai, and J.-D. Li
The Transforming Growth Factor-beta-Smad3/4 Signaling Pathway Acts as a Positive Regulator for TLR2 Induction by Bacteria via a Dual Mechanism Involving Functional Cooperation with NF-{kappa}B and MAPK Phosphatase 1-dependent Negative Cross-talk with p38 MAPK
J. Biol. Chem., August 4, 2006; 281(31): 22397 - 22408.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
T. Tsukuba, S. Yamamoto, M. Yanagawa, K. Okamoto, Y. Okamoto, K. I. Nakayama, T. Kadowaki, and K. Yamamoto
Cathepsin e-deficient mice show increased susceptibility to bacterial infection associated with the decreased expression of multiple cell surface toll-like receptors.
J. Biochem., July 1, 2006; 140(1): 57 - 66.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
K. A. Archer and C. R. Roy
MyD88-Dependent Responses Involving Toll-Like Receptor 2 Are Important for Protection and Clearance of Legionella pneumophila in a Mouse Model of Legionnaires' Disease.
Infect. Immun., June 1, 2006; 74(6): 3325 - 3333.
[Abstract] [Full Text] [PDF]

Home page
 Arch SurgHome page
L. Romics Jr, G. Szabo, J. C. Coffey, J. H. Wang, and H. P. Redmond
The Emerging Role of Toll-Like Receptor Pathways in Surgical Diseases
Arch Surg, June 1, 2006; 141(6): 595 - 601.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Esen and T. Kielian
Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns.
J. Immunol., June 1, 2006; 176(11): 6802 - 6811.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. Katz, P. Zhang, M. Martin, S. N. Vogel, and S. M. Michalek
Toll-Like Receptor 2 Is Required for Inflammatory Responses to Francisella tularensis LVS.
Infect. Immun., May 1, 2006; 74(5): 2809 - 2816.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
E. Szomolanyi-Tsuda, X. Liang, R. M. Welsh, E. A. Kurt-Jones, and R. W. Finberg
Role for TLR2 in NK Cell-Mediated Control of Murine Cytomegalovirus In Vivo
J. Virol., May 1, 2006; 80(9): 4286 - 4291.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. M. van der Sar, O. W. Stockhammer, C. van der Laan, H. P. Spaink, W. Bitter, and A. H. Meijer
MyD88 Innate Immune Function in a Zebrafish Embryo Infection Model
Infect. Immun., April 1, 2006; 74(4): 2436 - 2441.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Fan, Y. Li, Y. Vodovotz, T. R. Billiar, and M. A. Wilson
Hemorrhagic shock-activated neutrophils augment TLR4 signaling-induced TLR2 upregulation in alveolar macrophages: role in hemorrhage-primed lung inflammation
Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L738 - L746.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. K. Behera, E. Hildebrand, R. T. Bronson, G. Perides, S. Uematsu, S. Akira, and L. T. Hu
MyD88 Deficiency Results in Tissue-Specific Changes in Cytokine Induction and Inflammation in Interleukin-18-Independent Mice Infected with Borrelia burgdorferi
Infect. Immun., March 1, 2006; 74(3): 1462 - 1470.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
Y.-T.A. Teng
Protective and Destructive Immunity in the Periodontium: Part 1--Innate and Humoral Immunity and the Periodontium
Journal of Dental Research, March 1, 2006; 85(3): 198 - 208.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Knapp, C. W. Wieland, S. Florquin, R. Pantophlet, L. Dijkshoorn, N. Tshimbalanga, S. Akira, and T. van der Poll
Differential Roles of CD14 and Toll-like Receptors 4and 2 in Murine Acinetobacter Pneumonia
Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 122 - 129.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Yoshida, H. Jono, H. Kai, and J.-D. Li
The Tumor Suppressor Cylindromatosis (CYLD) Acts as a Negative Regulator for Toll-like Receptor 2 Signaling via Negative Cross-talk with TRAF6 and TRAF7
J. Biol. Chem., December 9, 2005; 280(49): 41111 - 41121.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. B. Su, P. B. Silver, R. S. Grajewski, R. K. Agarwal, J. Tang, C.-C. Chan, and R. R. Caspi
Essential Role of the MyD88 Pathway, but Nonessential Roles of TLRs 2, 4, and 9, in the Adjuvant Effect Promoting Th1-Mediated Autoimmunity
J. Immunol., November 15, 2005; 175(10): 6303 - 6310.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
T. Kielian, A. Haney, P. M. Mayes, S. Garg, and N. Esen
Toll-Like Receptor 2 Modulates the Proinflammatory Milieu in Staphylococcus aureus-Induced Brain Abscess
Infect. Immun., November 1, 2005; 73(11): 7428 - 7435.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. S. Hadley, J. E. Wang, S. J. Foster, C. Thiemermann, and C. J. Hinds
Peptidoglycan of Staphylococcus aureus Upregulates Monocyte Expression of CD14, Toll-Like Receptor 2 (TLR2), and TLR4 in Human Blood: Possible Implications for Priming of Lipopolysaccharide Signaling
Infect. Immun., November 1, 2005; 73(11): 7613 - 7619.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Mikami, H. Gu, H. Jono, A. Andalibi, H. Kai, and J.-D. Li
Epidermal Growth Factor Receptor Acts as a Negative Regulator for Bacterium Nontypeable Haemophilus influenzae-induced Toll-like Receptor 2 Expression via an Src-dependent p38 Mitogen-activated Protein Kinase Signaling Pathway
J. Biol. Chem., October 28, 2005; 280(43): 36185 - 36194.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. Fuse, G. Chan, Y. Liu, P. Gudgeon, M. Husain, M. Chen, W.-C. Yeh, S. Akira, and P. P. Liu
Myeloid Differentiation Factor-88 Plays a Crucial Role in the Pathogenesis of Coxsackievirus B3-Induced Myocarditis and Influences Type I Interferon Production
Circulation, October 11, 2005; 112(15): 2276 - 2285.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
M. G. Netea, J. W. M. Van der Meer, R. P. Sutmuller, G. J. Adema, and B.-J. Kullberg
From the Th1/Th2 Paradigm towards a Toll-Like Receptor/T-Helper Bias
Antimicrob. Agents Chemother., October 1, 2005; 49(10): 3991 - 3996.
[Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. Srivastava, P. Henneke, A. Visintin, S. C. Morse, V. Martin, C. Watkins, J. C. Paton, M. R. Wessels, D. T. Golenbock, and R. Malley
The Apoptotic Response to Pneumolysin Is Toll-Like Receptor 4 Dependent and Protects against Pneumococcal Disease
Infect. Immun., October 1, 2005; 73(10): 6479 - 6487.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
V. Balloy, M. Si-Tahar, O. Takeuchi, B. Philippe, M.-A. Nahori, M. Tanguy, M. Huerre, S. Akira, J.-P. Latge, and M. Chignard
Involvement of Toll-Like Receptor 2 in Experimental Invasive Pulmonary Aspergillosis
Infect. Immun., September 1, 2005; 73(9): 5420 - 5425.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Naiki, K. S. Michelsen, N. W. J. Schroder, R. Alsabeh, A. Slepenkin, W. Zhang, S. Chen, B. Wei, Y. Bulut, M. H. Wong, et al.
MyD88 Is Pivotal for the Early Inflammatory Response and Subsequent Bacterial Clearance and Survival in a Mouse Model of Chlamydia pneumoniae Pneumonia
J. Biol. Chem., August 12, 2005; 280(32): 29242 - 29249.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H.-S. Mun, F. Aosai, K. Norose, L.-X. Piao, H. Fang, S. Akira, and A. Yano
Toll-Like Receptor 4 Mediates Tolerance in Macrophages Stimulated with Toxoplasma gondii-Derived Heat Shock Protein 70
Infect. Immun., August 1, 2005; 73(8): 4634 - 4642.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Fan, B. Zingarelli, O. M. Peck, G. Teti, G. E. Tempel, P. V. Halushka, and J. A. Cook
Lipopolysaccharide- and gram-positive bacteria-induced cellular inflammatory responses: role of heterotrimeric G{alpha}i proteins
Am J Physiol Cell Physiol, August 1, 2005; 289(2): C293 - C301.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
B. Fournier and D. J. Philpott
Recognition of Staphylococcus aureus by the Innate Immune System
Clin. Microbiol. Rev., July 1, 2005; 18(3): 521 - 540.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Omatsu, T. Iyoda, Y. Kimura, A. Maki, M. Ishimori, N. Toyama-Sorimachi, and K. Inaba
Development of Murine Plasmacytoid Dendritic Cells Defined by Increased Expression of an Inhibitory NK Receptor, Ly49Q
J. Immunol., June 1, 2005; 174(11): 6657 - 6662.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Henneke, S. Morath, S. Uematsu, S. Weichert, M. Pfitzenmaier, O. Takeuchi, A. Muller, C. Poyart, S. Akira, R. Berner, et al.
Role of Lipoteichoic Acid in the Phagocyte Response to Group B Streptococcus
J. Immunol., May 15, 2005; 174(10): 6449 - 6455.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. G. Netea, G. Ferwerda, D. J. de Jong, T. Jansen, L. Jacobs, M. Kramer, T. H. J. Naber, J. P. H. Drenth, S. E. Girardin{paragraph}, B. Jan Kullberg, et al.
Nucleotide-Binding Oligomerization Domain-2 Modulates Specific TLR Pathways for the Induction of Cytokine Release
J. Immunol., May 15, 2005; 174(10): 6518 - 6523.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. W. Chu, S. Jeyaseelan, J. G. Rino, D. R. Voelker, R. B. Wexler, K. Campbell, R. J. Harbeck, and R. J. Martin
TLR2 Signaling Is Critical for Mycoplasma pneumoniae-Induced Airway Mucin Expression
J. Immunol., May 1, 2005; 174(9): 5713 - 5719.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Rodriguez, F. Fend, L. Jennen, M. Schiemann, N. Wantia, C. U. P. da Costa, S. Durr, U. Heinzmann, H. Wagner, and T. Miethke
Polymorphonuclear Neutrophils Improve Replication of Chlamydia pneumoniae In Vivo upon MyD88-Dependent Attraction
J. Immunol., April 15, 2005; 174(8): 4836 - 4844.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
E. Lorenz, D. C. Chemotti, A. L. Jiang, and L. D. McDougal
Differential Involvement of Toll-Like Receptors 2 and 4 in the Host Response to Acute Respiratory Infections with Wild-Type and Mutant Haemophilus influenzae Strains
Infect. Immun., April 1, 2005; 73(4): 2075 - 2082.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. L. Kau, S. M. Martin, W. Lyon, E. Hayes, M. G. Caparon, and S. J. Hultgren
Enterococcus faecalis Tropism for the Kidneys in the Urinary Tract of C57BL/6J Mice
Infect. Immun., April 1, 2005; 73(4): 2461 - 2468.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
G. I Lancaster, Q. Khan, P. Drysdale, F. Wallace, A. E Jeukendrup, M. T Drayson, and M. Gleeson
The physiological regulation of toll-like receptor expression and function in humans
J. Physiol., March 15, 2005; 563(3): 945 - 955.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
B. Gonzalez-Zorn, J. P. M. Senna, L. Fiette, S. Shorte, A. Testard, M. Chignard, P. Courvalin, and C. Grillot-Courvalin
Bacterial and Host Factors Implicated in Nasal Carriage of Methicillin-Resistant Staphylococcus aureus in Mice
Infect. Immun., March 1, 2005; 73(3): 1847 - 1851.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
H. Bjorkbacka, K. A. Fitzgerald, F. Huet, X. Li, J. A. Gregory, M. A. Lee, C. M. Ordija, N. E. Dowley, D. T. Golenbock, and M. W. Freeman
The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades
Physiol Genomics, February 7, 2005; 19(3): 319 - 330.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takeuchi, O.
Right arrow Articles by Akira, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takeuchi, O.
Right arrow Articles by Akira, S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS